Tertiary phosphines find utility in several areas of organic chemistry, for example as starting materials for making phosphonium salts and ylids and as ligands in metal-carbene catalysts.
Some bulky tertiary phosphines, such as tricyclohexylphosphine, have been reported to be useful as catalyst ligands. For example, bulky tertiary phosphines find utility as ligands for metal catalysts, such as the ruthenium-based Grubbs catalyst (named after its inventor, Robert H. Grubbs). Notably, metal-carbene catalysts having tertiary phosphine ligands can be used as catalysts in several types of reactions, including: olefin metathesis reactions (for a recent review, see Rouhi, A. M. (2002) Chemical and Engineering News. pp. 29-33; see also: Grubbs et al. (1995) Acc. Chem. Res., vol. 28, p. 446-452; Grubbs et al. (1998) Tetrahedron, vol. 54, pp. 4413-4450; Chatterjee et al. (1999) Org. Lett. Vol. 1, pp. 1751-1753); palladium-catalysed Suzuki cross couplings (Nethrton et al. (2001) J. Am. Chem. Soc., vol. 123, pp. 10099-10100; Littke et al. (2000) J. Am. Chem. Soc., vol. 122, pp. 4020-4028); and palladium-catalysed Heck reactions (A. F. Littke and G. C. Fu, (1999) J. Org. Chem., vol. 64, pp. 10-11; Cabri et al. (1995) Acc. Chem. Res., vol. 28, pp. 2-7).
A variety of tertiary phosphines can be prepared by reacting phosphorus trichloride with a Grignard reagent or with an organolithium compound, followed by aqueous workup, extraction and distillation. However, these processes have several disadvantages, in that materials used in these processes are expensive, corrosive, difficult to prepare owing to their sensitivity to moisture, and cumbersome to handle on a large scale. In addition, these processes generate large amount of waste. Further, these processes usually proceed quickly to the tertiary phosphine and are ideal for preparing a tertiary phosphine having identical radicals but are less suitable for preparing a tertiary phosphine having a particular composition of non-identical radicals.
Alternatively, phosphine gas (PH3) can be reacted with an alkene under free radical conditions to produce primary, secondary and tertiary phosphines. This process advantageously avoids the use of organometallic compounds. However, this process may be less suitable for producing certain tertiary phosphines, such as tertiary phosphines that have several sterically bulky radicals attached to the central phosphorus atom. For example, addition of cyclohexene to PH3 under free radical conditions favours the production of dicyclohexylphosphine and provides poor yields of tricyclohexylphosphine.
There have been some reports in the literature describing the preparation of cyclic and bicyclic tertiary phosphines (i.e. where the phosphorus atom is a ring member in a cyclic or bicyclic structure, respectively) via double Michael-additions of primary phosphines to conjugated dienones (Y. Kashman and Benady, E. (1972) Tetrahedron, vol. 28, pp. 4091-4098; E. Y. Zabotina et al. (2001) Tetrahedron, vol. 57, pp. 10177-10180; and WO 02/064249). However, this approach is limited to the preparation of cyclic and bicyclic phosphines.